Cancer Treatment Today

Abraxane (nab-paclitaxel) is an albumin-bound, 130-nm particle form of paclitaxel that was developed to avoid cremophor/ethanol-associated toxicities associated with the parent compound. Abraxane is FDA-approved for the treatment of breast cancer after the failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Abraxane has been evaluated as a single agent in chemotherapy-naïve patients with advanced and metastatic NSCLC by Rizvi et al.[6] In this study the MTD for Abraxane administered over 30 min. on days 1, 8, and 15 on a 28 day cycle was 125 mg/m2. Premedication with dexamethasone was not required, and no hypersensitivity reactions were observed. In the extended phase II part of the study a 30% response rate and 10.9 month survival was achieved among 40 patients entered. Fatigue and sensory neuropathy were the most frequently reported toxicities resulting in discontinuation of the agent in 18 patients (45%). Nail changes and edema were other rare toxicities, and diarrhea was mild and easily manageable.

Single agent Abraxane has also been evaluated at a dose of 260 mg/m2 over 30 minutes every 3 weeks in chemotherapy-naïve patients with advanced and metastatic NSCLC.  Overall it was well-tolerated. Grade 3 neuropathy occurred in 2 patients after > 6 cycles. The response rate was 16% with a median TTP of 6 months and a MST of 11 mos. There are phase II studies with carboplatin.

Ongoing and future strategies with Abraxane include combinations with novel targeted agents and incorporation into the management of early-stage NSCLC. It appears that weekly Abraxane may have a better therapeutic index than an every-3-week regimen and the data in NSCLC with Abraxane has been consistent across studies. Abraxane and gemcitabine have been studied in breast cancer and was recently found to be effective for pancreatic cancer but I did not find any trials for lung cancer.

Rizvi N, Azzoli C, Miller V, et al. Phase I/II study of ABI-007 as first line chemotherapy in advanced non-small cell lung cancer. J Clin Oncol 2006;24:Abstract # 7105.

Green MR, Manikhas GM, Orlov S, et al. Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol 2006;17:1263-1268.

Hawkins MJ, Georgy M, Makhson A, et al. Dose escalation study of nab-paclitaxel followed by carboplatin as first-line therapy in advanced non-small cell lung cancer. J Clin Oncol 2006;24: 397s, Abstract # 7132.

Allerton JP, Hagenstad CT, Webb RT, et al. A phase II evaluation of the combination of paclitaxel protein-bound and carboplatin in the first-line treatment of advanced non-small cell lung cancer. J Clin Oncol 2006;24:395s, Abstract # 7127.

Sandler A, Gray R, Perry MC, et al: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542-2550.

Reynolds C, et al. Nab-Paclitaxel/Carboplatin/Bevacizumab in Advanced Non-Squamous NSCLC. Proceedings of the Chemotherapy Foundation Symposium XXIV. New York, New York. November 12, 2006.

Greco A, et al. Albumin Bound Paclitaxel Wkly+Carboplatin: First-Line Therapy for Advanced NSCLC. Proceedings of the Chemotherapy Foundation Symposium XXIV. New York, New York. November 12, 2006.

Mark A. Socinski,Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced NonSmall-Cell Lung Cancer: Final Results of a Phase III Trial JCO June 10, 2012 vol. 30 no. 17 2055-2062